The effect of surgical prehabilitation on autonomic nervous system regulation: Rationale and design of the TUNE trial

Prehabilitation improves physiological readiness for major surgery; however, its implementation and evaluation remain inconsistent, particularly in thoracic surgery. Current assessments largely rely on functional tests, which are difficult to standardize and provide limited knowledge of biological resilience. Heart-rate variability (HRV) is an objective marker of autonomic nervous system balance and is already widely used in sports medicine to guide training intensity and evaluate the relationship between physiological stress and recovery. Given its ability to capture the dynamicity and flexibility of autonomic regulation, HRV may become a practical tool to assess the physiological effects of prehabilitation interventions, going beyond traditional endpoints.

The TUNE trial is a multicenter, open label, randomized controlled trial involving patients scheduled for elective major thoracic surgery. Participants are randomized in a 1:1 ratio to receive either a home-based multimodal prehabilitation program in addition to standard care or standard care alone. The intervention consists of a 4 week remotely delivered program including structured physical exercise, personalized nutritional optimization and psychological support.

The trial is ongoing and currently recruiting participants. The primary endpoint is the between-group difference in the change of HRV, measured as the standard deviation of normal-to-normal intervals (SDNN), from baseline to preoperative assessment. Secondary outcomes include correlations between HRV and clinical outcomes.

The TUNE trial will provide data to assess whether a prehabilitation program can improve HRV and facilitate recovery in patients undergoing major thoracic surgery.

This trial was registered on ClinicalTrials.gov with the trial identification NCT06398301.